Chordomas are primary malignant tumors of the spinal column as well as the skull base (1-5). These are rare malignancies with an incidence of 0.8 per 100,000 (4). Chordomas arise from intraosseous notochordal cell remnants and are commonly found in the sacrum (55%), spheno-occipital region (35%) and mobile spine (15%) (4). In the mobile spine and sacrum, the primary surgical treatment of chordoma is en-bloc resection, if feasible (6-12). This is often followed by radiation treatment, preferably proton-beam radiation if available or high-dose conventional radiation treatment of 60 Gy or higher (13,14). Identifying the most impactful scientific articles addressing chordomas can benefit patient care and research of this rare malignancy. Our objective was to identify the top 50 cited articles on chordomas and to further analyze characteristics of these top 50 cited articles.
The study design is a bibliometric analysis in March of 2017, we used ISI Web of Science (v5.11, Thomas Reuter, Philadelphia, Pennsylvania, USA) to search for the following key word: “chordoma”. Search areas included orthopedics, neurosurgery, radiology, oncology, rehabilitation, surgery, and nuclear medicine and imaging. Articles were searched from 1900 to 2017.
Articles were ranked based on number of citations. The results were subsequently evaluated to determine articles most clinically relevant to the management of chordomas. The top 50 articles that met the search criteria were further characterized on the basis of: title, author, citation density, journal of publication, year (and decade) of publication, institution and country of origin and paper topic.
The most influential articles (Table 1)
A total of 1,043 articles matched the search criteria. The most influential 50 articles ranged from 65 to 290 in number of citations. The articles were published between 1926 and 2012, and all articles were published in English. The top cited article was the 2001 work by McMaster et al. delineating the incidence and survival rate of chordoma patients in the United States (4). The second most cited article was published in 1952 by Dahlin et al. and discussed 59 chordoma cases from a single institution (15). Third on the list was the article by Higinbotham et al. on a 35-year single center experience with the management of chordomas (16).
Country of origin (Table 2)
Thirty-three publications (66%) originated from the United States, 7 (14%) from Italy, 4 (8%) from the United Kingdom and 3 (6%) from Japan (Table 2).
Destination journals (Table 3)
Cancer accounted for the most frequent (n=9) destination journal. The second most common destination journal was Journal of Bone and Joint Surgery (n=4). The following four journals published three articles each: Spine, International Journal of Radiation Oncology Biology Physics, Archives of Pathology & Laboratory Medicine and American Journal of Surgical Pathology.
Decade of publication (Table 4)
The 2000s was the most active decade of publication (17 papers) followed by 1980s with twelve articles published in that decade. This was followed by the 1990s with eight articles and the 1970s with four articles.
Most frequently cited authors (Table 5)
There were three top published authors: Boriani S with two articles, Casali PG with two articles and Meis JM with two articles.
Most frequently cited institutions (Table 6)
A total of 41 institutions contributed to the top 50 articles. Massachusetts General Hospital contributed the most with four articles followed by the University of Texas M.D. Anderson Cancer Center with three publications and the Memorial Sloan-Kettering Cancer Center with three publications as well. The Istituto Nazionale e la Cura dei Tumori from Milan Italy contributed two publications as well as the University of Pittsburgh with two articles.
Paper topics (Table 7)
The most common article type was clinical 44% (n=22), followed by papers that combined clinical and pathology findings 18% (n=9), basic science research 14% (n=7), radiation treatment research 10% (n=5), pathology-related research 8% (n=4) and chemotherapy research 6% (n=3).
Chordomas are rare malignant primary tumors of the spinal column and spheno-occipital region that are managed by a multi-disciplinary team encompassing orthopedic surgery, neurosurgery, radiation oncology and medical oncology (13). Initially, best practices in the management of chordomas were predominantly driven by single institution studies with multi-center studies becoming more prominent over the past decade (1,15,16). Aside from those orthopaedic surgeons and neurosurgeons who have sought out additional training in spine oncology, most spine tumor surgery is performed by spine surgeons taking call or in academic centers affiliated with cancer centers. However, chordomas of the mobile spine and sacrum often require en-bloc resections and should ideally be managed by centers with experience in this technique (1,2,5). In the setting of a multi-disciplinary a better understanding of the top cited papers that are driving advances in chordoma research are needed.
The most cited article was the 2001 work by McMaster et al. delineating the incidence and survival rate of chordoma patients in the United States (4). This was published in Cancer Causes Control and cited 290 times. The authors used the Surveillance, Epidemiology, and End Results (SEER) database from the National Cancer Institute to query 400 chordoma cases from 1973 to 1995. The authors noted an incidence rate (IR) of 0.08 per 100,000 and more common in males, patients older than 40, males and whites. They noted 32% of cases were cranial, 32.8% in the mobile spine and 29.2% in the sacrum. Cranial presentation was associated with age <26 years and females. Lastly, they noted a 5-year survival rate of 67.6% and 10-year survival rate of 39.9%.
The second most cited article was published in 1952 by Dahlin et al. in the journal Cancer and reports on 59 cases of chordoma from the Mayo Clinic (15). The first case was from 1910 and the last case was from 1951. The series included 41 males and 18 females. Fifteen cases (25.4%) were at the spheno-occipital region, 54.2% (n=32) in the sacrum and 20.3% (n=12) in the mobile spine. Pain and constipation were common presentations of sacral chordomas. Surgical intervention included en-bloc excision followed by radiation treatment. Chordomas in the spheno-occipital region presented with visual disturbances and headaches. Mobile spine chordomas in this series presented at later stages with cord symptoms and nerve root symptoms. However, there were no attempts in that era of en-bloc excisions and most patients had poor prognosis following radiation and debulking procedures.
Third on the list is the 1967 article by Higinbotham et al. which reports a single center series on the management of chordomas over a 35-year period (16). These were 46 cases from 1930 to 1965, with 30 (65.2%) sacral chordomas, 10 (21.7%) in the mobile spine and 6 (13.0%) in the spheno-occipital. Most patients were male (n=32) and 43% of patients had metastases at presentation. Patients with sacrococcygeal chordomas presented with palpable rectal masses and received a combination of radiation or surgical intervention followed by radiation treatment. In the ten cases of the mobile spine, 5 were in the cervical, 3 in the lumbar and 2 in the thoracic spine. Axial pain was a common presenting symptom followed by neurological signs and symptoms. Delayed diagnosis was present due to symptoms being attributed to other etiologies.
The highly cited paper is by Stacchiotti et al. published in 2012 (17). The study is a phase 2 trial evaluating the role of Imatinib, a tyrosine kinase inhibitor for the management of chordomas. The authors enrolled 56 patients in a multicenter trial. In order to enroll, patients had to have expression of platelet-derived growth factor receptor β (PDGFRB) and/or platelet-derived growth factor β. The demographics included 35 males (62.5%) and location of the tumor were predominantly in the sacrum (58.9%) followed by 25% in the mobile spine and 16.1% in the skull base. The study demonstrates Imatinib had some anti-tumor activity against chordoma and is currently used by some centers for the treatment of chordomas.
The oldest highly cited paper is the 1926 article by Stewart et al. which is a review article and also a case report of sacrococcygeal chordoma (18). Dr. Stewart was a pathologist at the University of Leeds and describes the case of 58-year-old male with a sacrococcygeal chordoma, including the relevant pathology. The article also provides a review of other chordoma cases and their respective presentation, pathology and management.
The most common topic among the top 50 cited articles was the clinical management of chordomas (n=22). This was followed by articles combining pathology and clinical presentation (n=9), basic science articles (n=7), radiation therapy articles (n=5), pathology articles (n=4) and chemotherapy related articles (n=3). The distribution of article types is representative of the fact that most chordomas are addressed surgically followed by radiation treatment. However, basic science studies such as the first description of brachyury as a biomarker of chordoma and other papers that are pertinent to brachyury are also represented in the top 50 cited list.
Centers from the United States had the most studies cited in the top 50 followed by centers from Italy. Cancer was the most common publication journal. The fact that Cancer was the journal with the most (18%) top 50 citations is indicative of the multi-disciplinary nature of chordoma management. The 2000s were the most productive decade followed by the 1980s. Three authors: Boriani S (Italy), Casali PG (Italy) and Meis JM (United States) were the most cited.
There are some limitations to our study. The first limitation is the fluid nature of citations. Our search was conducted in March 2017 and since then the citation numbers would have changed. However, the trend of the top cited papers would be unlikely to have dramatically changed. The other limitation is citations may be dependent on how often a journal is published. For example, a weekly journal is more likely to publish more papers and subsequent citations as compared to a journal published quarterly. Our search is also limited to English language studies and there is a possibility we may have not included non-English language cited that were highly cited.
In conclusion, in this first study evaluating the most impactful and highly cited chordoma articles we found most of the articles were clinical papers, arising from the United States. These articles were most frequently published in Cancer and Journal of Bone and Joint Surgery. Most of these papers were published in the 2000s. In order to advance research and treatment for chordomas it is important to understand the current top cited articles on this rare malignancy. With further advances and breakthroughs in this field it would be worthwhile to revisit the question of top cited chordoma articles in the future and in this article, we have described the current state of the most impactful chordoma articles.
Conflicts of Interest: The authors have no conflicts of interest to declare.
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